An acidic polysaccharide (APS) was isolated from the extract of Cordyceps militaris grown on germinated soybeans. Analyses of sugar composition indicated that APS consisted of d-galactose, L-arabinose, D-xylose, L-rhamnose, and D-galacturonic acid. On the basis of the result of methylation analysis, APS was considered to be mainly composed of Araf-(1-->, -->5)-Araf-(1-->, -->4)-Galp-(1--> and -->4)-GalAp-(1--> residues. When the polysaccharide was intranasally administered, it decreased virus titers in the bronchoalveolar lavage fluid and the lung of mice infected with influenza A virus and increased survival rate. Furthermore, APS increased TNF-alpha and IFN-gamma levels in mice when compared with those of untreated mice. APS enhanced nitric oxide (NO) production and induced iNOS mRNA and protein expressions in RAW 264.7 murine macrophage cells. The induction of mRNA expression of cytokines including IL-1beta, IL-6, IL-10, and TNF-alpha was also observed. These results demonstrated that APS might have beneficial therapeutic effects on influenza A virus infection at least in part by modulation of the immune function of macrophages.